Dataset Information

MicrobiomeDASim: Simulating longitudinal differential abundance for microbiome data.

ABSTRACT: An increasing emphasis on understanding the dynamics of microbial communities in various settings has led to the proliferation of longitudinal metagenomic sampling studies. Data from whole metagenomic shotgun sequencing and marker-gene survey studies have characteristics that drive novel statistical methodological development for estimating time intervals of differential abundance. In designing a study and the frequency of collection prior to a study, one may wish to model the ability to detect an effect, e.g., there may be issues with respect to cost, ease of access, etc. Additionally, while every study is unique, it is possible that in certain scenarios one statistical framework may be more appropriate than another. Here, we present a simulation paradigm implemented in the R Bioconductor software package microbiomeDASim available at http://bioconductor.org/packages/microbiomeDASim microbiomeDASim. microbiomeDASim allows investigators to simulate longitudinal differential abundant microbiome features with a variety of known functional forms with flexible parameters to control desired signal-to-noise ratio. We present metrics of success results on one particular method called metaSplines.

SUBMITTER: Williams J

PROVIDER: S-EPMC7047923 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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<i>microbiomeDASim</i>: Simulating longitudinal differential abundance for microbiome data.

Williams Justin J Bravo Hector Corrada HC Tom Jennifer J Paulson Joseph Nathaniel JN

F1000Research 20191017

An increasing emphasis on understanding the dynamics of microbial communities in various settings has led to the proliferation of longitudinal metagenomic sampling studies. Data from whole metagenomic shotgun sequencing and marker-gene survey studies have characteristics that drive novel statistical methodological development for estimating time intervals of differential abundance. In designing a study and the frequency of collection prior to a study, one may wish to model the ability to detect ...[more]

PMID: 32148761

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Project description:MotivationMicrobial communities have been proved to have close relationship with many diseases. The identification of differentially abundant microbial species is clinically meaningful for finding disease-related pathogenic or probiotic bacteria. However, certain characteristics of microbiome data have hurdled the accuracy and effectiveness of differential abundance analysis. The abundances or counts of microbiome species are usually on different scales and exhibit zero-inflation and over-dispersion. Normalization is a crucial step before the differential abundance test. However, existing normalization methods typically try to adjust counts on different scales to a common scale by constructing size factors with the assumption that count distributions across samples are equivalent up to a certain percentile. These methods often yield undesirable results when differentially abundant species are of low to medium abundance level. For differential abundance analysis, existing methods often use a single distribution to model the dispersion of species which lacks flexibility to catch a single species' distinctiveness. These methods tend to detect a lot of false positives and often lack of power when the effect size is small.ResultsWe develop a novel framework for differential abundance analysis on sparse high-dimensional marker gene microbiome data. Our methodology relies on a novel network-based normalization technique and a two-stage zero-inflated mixture count regression model (RioNorm2). Our normalization method aims to find a group of relatively invariant microbiome species across samples and conditions in order to construct the size factor. Another contribution of the paper is that our testing approach can take under-sampling and over-dispersion into consideration by separating microbiome species into two groups and model them separately. Through comprehensive simulation studies, the performance of our method is consistently powerful and robust across different settings with different sample size, library size and effect size. We also demonstrate the effectiveness of our novel framework using a published dataset of metastatic melanoma and find biological insights from the results.Availability and implementationThe R package 'RioNorm2' can be installed from Github athttps://github.com/yuanjing-ma/RioNorm2.Supplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

MicrobiomeDASim: Simulating longitudinal differential abundance for microbiome data.

Publications

<i>microbiomeDASim</i>: Simulating longitudinal differential abundance for microbiome data.

Similar Datasets

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